Permanent Impairment of Testicular Development After Transient Immunological Blockade of Endogenous Luteinizing Hormone Releasing Hormone in the Neonatal Rat

In order to evaluate the role of luteinizing hormone-releasing hormone (LHRH) in the development of gonadal function in the male rat, groups of animals were injected ip at age 1, 5, 10, 15, and 34 days with a single dose of a high potency antiserum from a rabbit immunized with LHRH. Testicular size achieved at 100 days was significantly reduced in all except animals treated at 34 days of age. In rats treated on day 1 or 5, the penis and seminal vesicles were also smaller. A separately studied group injected with antiserum to LHRH (LHRH-AS) on the 10th day of life and sacrificed 7 days later also showed decreased testicular size. Histological examination of the testes on the 100th day in LHRH-AS treated rats showed decreased seminiferous tubular diameter. When tested at age 70 to 100 days, fertility of rats treated on day 5 was markedly reduced. Although tubular function was apparently impaired by early treatment with antibody, serum levels of testosterone, LH and FSH, and prolactin determined on day 100 were normal as was mating behavior, studied between 75 and 85 days of life. These studies indicate that the normal development of pituitary-gonadal function requires the presence of LHRH from day 1 of age. Infertility and reduced testis size long after acute antibody neutralization effects have dissipated suggest that early postnatal life is a “critical period” for testicular differentiation and is dependent upon the integrity of hypothalamic-pituitary function.